The application of siRNA to medical treatments is increasingly expected because siRNA can knock down target mRNA specifically and effectively. However, the development of an effective delivery system is indispensable to applying siRNA to medical treatments. In recent years, it has been clarified in clinical trials that the therapeutic effect on age-related macular degeneration (CNV) by intraocular administration of naked siRNA does not result from a sequence-specific gene knockdown effect mediated by siRNA, but rather results from a non-sequence-specific effect via recognition by the cell surface Toll-like receptor-3 (TLR-3); thus, the development of a carrier, which is stable outside of cells and is capable of accurately delivering siRNA into the cells in any in vivo application of siRNA, is considered to be important.
Thus far, a variety of cationic polymers have been provided as carriers for forming a polyion complex (PIC) with DNA and for introducing and expressing the nucleic acid into eukaryotic cells. For example, it is known that a poly(L-lysine) derivative in which a hydrophilic group (e.g., polyethylene glycol) and a hydrophobic group (e.g., a palmitoyl group) have been introduced via an ε-amino group of poly (L-lysine) forms a vesicle in the presence of cholesterol in an aqueous medium, and the vesicle aggregates gene-containing plasmid DNA to form a stable complex (Patent Literature 1). Further, a PIC formed of plasmid DNA with a copolymer derivative whose cation charge and disulfide cross-link density have been adjusted by the thiolation of an ε-amino group of poly (L-lysine) in a poly (L-lysine)-poly (ethylene glycol) copolymer is known to show high stability in an extracellular medium and to effectively release the DNA in an intracellular compartment (Non Patent Literature 1). Further, it has been confirmed that, when poly(N—[N-(2-aminoethyl)-2-aminoethyl]aspartamide (pAsp (DET))) having an ethylenediamine structure in a side chain and a block copolymer including the pAsp (DET) as one block component of the block copolymer are produced, such polymers exhibit low cytotoxicity and introduce plasmid DNA into cells with high efficiency to efficiently express a gene incorporated into the DNA (see Non Patent Literature 2, Patent Literature 2, and Patent Literature 3).
As described above, although a carrier effective for a high molecular weight nucleic acid such as DNA has been developed, a carrier capable of also forming a stable complex such as a PIC with a low molecular weight nucleic acid such as siRNA under physiological conditions and capable of suitably releasing the low molecular weight nucleic acid in cells has not been provided yet.